ER Rx: Patient received 2 L NS bolus, and in 4 hrs, Na increased to 120. Patient voided significant amount of Urine during that time. The rate of correction was rapid that it had to be. What went wrong?

Case 3: Hypervolumic: Same patient

U Na is 10. U -Osm 400. BP is 100/60. HR 115. But has significant asicitis, and 2 + edema in leg (decompensated cirrhosis)ER Rx: Patient received 2 L NS bolus, and in 4 hrs, Na increased to 115, but patient retained all the fluid and made the edema worse. Patient fluid status got worse. What went wrong?

5 Overall Concepts1. Define Etiology (ADH mediated or NOT, Mechanism of ADH generation, Aldo is high or NOT)2. Define Risk of ODS or CPD and Treatment goal3. Treatment strategy depends on Etiology and acuity4. Plasma Na is a function of total body Na and K and Water5. Balance of Electrolytes "IN/L of fluid given" and "Electrolyte OUT/L of Urine Output" will define if Plasma Na is going to increase or not - i.e Understand the concept of Hypotonic Urine (more free water loss in Urine) in correction of hyponatremia.

HYPERNATREMIA: Na: High: Problem is with Free Water Deficit (i.e. dehydration, which is different from salt and water loss i e. hypovolumia) 2/2: Calculate Urine and Serum Osmolality - Calculate TOTAL Free Water Deficit (target Na of 140) - Calculate Water Deficit to replete in next 24 hour (with goal of no more than 10 mEq /day) -Calculate the rate of repleting D5W (free water) over 24 hour -If patient is symptomatic due to volume loss, give normal saline bolus to avoid rapid sodium correction during fluid repletion

Ans: More free water loss than sodium in Loop Diuretics, and more Sodium Loss compared to free water in Thiazides.

Both case due to fluid loss have more ADH, and Aldosterone. Both act distal to where Loop and Thiazide Diuretics act. Then why such a different in fluid loss in two situations.

Ans: Na K 2Cl- Channel that loop diuretics block is needed to maintain the medullary concentration gradient. NaCl- channels that thiazides blocks does not have much role in medullary gradient. Medullary gradient is needed for ADH to retain free water. In the absence of gradient, even though there is plenty of ADH, no free water is retained in loop diuretics use, whereas that free water is retained with thiazide diuretics. Free water retention causes hyponatremia in Thiazide. Free water loss causes hypernatremia in Loop Diuretics.

What effect does ADH do on NK2Cl- channels?

Increases the rate of expression of these channels - both short term, and long term. NEJM 2015

How does oxcarbamazepine cause hyponatremia?

What is Urine Osmolality in Euvolumic Hyponatremia? U-Na?

U-Som is High due to high ADH (SIADH). U-Na is high as low aldo causes loss of U-Na.

Clinical Question

22 yo M patient with Schizophrenia was seen for fall. Was found to have S-Na of 113. S-osm was 240. U-osm is 46. U-Na is 6.

Describe the pathophysiology of Hyponatremia in this patient?

1. Low ADH: Hence, U-osm is low.

2. Hyponatremia is due to lack of enough Salt to drive out the water from body. Hence, it is as low as it can be.

This is a perfect example of hyponatremia due to Primary Polydipsia.

How would you treat this patient?

1. Fluid restriction.

2. Salt repletion.

Ans: While fluid restriction alone with regular diet (that has salt) will work, Salt repletion is the best answer, as that can drive out the water. This is highly affective since ADH is very low. Do not replete a lot of salt, as that will lead to rapid diuresis, and rapid correction of S-Na.

He also had hypokalemia when he presented. He was given NS at 75 cc / hr,

At, around 4 am, it was 116. Hence, IV fluid was changed to 1/2NS with K+. Fluid continued at 75 cc / hr.

Subsequent changes are as above. At, 730 am it was changed to 1/4 NS with K+. Na, continued to increase.

What could have been done upfront to minimize the risk of such a rapid correction of Na.

Ans:

1) Instead of 75 c / hr, NS could have been run at 25 cc / hr. That limits amount of Na, and amount of diuresis it can cause, and decreases the rate of correction.

2) At 730 am, since Na continued to go up, instead of changing the 1/4NS with K+, it should have been changed fully to D5, and needed to be given at a rate more than what kidney can handle. i.e @ 250 cc / hr. That would cause hyponatremia, and make sure it reverses.

What is the role of S-K+ in hyponatremia, and how does its correction affect S-Na.

Further explanation on how hypokalemia causes hyponatremia, and how potassium repletion causes correction of hyponatremia.

Hypokalemia is an independent predictive factor for the development of hyponatremia. Because intracellular and extracellular osmolality
are always equal, loss of either sodium or potassium, unless accompanied by loss of water, would
result in hypotonicity. Although it is intuitively
evident why changes in body sodium and water
levels should determine serum sodium concentration, the role of potassium is less obvious, but nevertheless is very important. Edelman et al showed that serum sodium
concentration is a function not only of total
exchangeable sodium and total-body water, but
also of total exchangeable potassium. The primary mechanism is that potassium depletion results in a shift of sodium into the cell with a
commensurate exit of potassium from the cell into
extracellular fluid. The reverse occurs during
potassium repletion and explains Laragh’s observation that oral potassium chloride administration
resulted in an increase in serum sodium levels in hyponatremic patients in the absence of administered sodium. A similar observation was reported
by Fichman et alin patients with diuretic-induced
hyponatremia and hypokalemia. This effect of
potassium repletion to increase serum sodium
concentration may be enhanced by the entry of
chloride into cell along with the potassium, which
renders the cell hypertonic and draws water from
the extracellular fluid.Potassium entry also may
be accompanied by the movement of hydrogen
ions from the intracellular to extracellular space,
where they are buffered and thereby made osmotically inactive. This would decrease effective
extracellular tonicity, again causing water to move
into the cells, increasing the extracellular concentration of sodium. Whichever mechanism is dominant, the important observation is that potassium
depletion could be associated with hyponatremia, and potassium repletion results in an increase in serum sodium concentration.